Most genera of new world primates exhibit vitamin D resistance. This resistance is biochemically characterized by the maintenance of a high circulating concentration of the active vitamin D hormone 1,25 dihydroxyvitamin D(1,25-(OH)2D) and the prohormone 25-hydroxyvitamin D(25-OHD). Clinical manifestations of vitamin D resistance include rickets in rapidly growing adolescent animals deprived of adequate sunlight exposure. Old world primates, including humans, do not exhibit vitamin D resistance. Levels of 25-OHD may be as much as ten fold lower, and levels of 1,25-(OH).sub.2 D as much as 100 fold lower, in old world primates than those observed in most new world primates. Vitamin D resistance phenomenon in new world primates also correlates with high circulating levels of other steroid hormones including glucocorticoid (Chrousos et al. Endocrinology 115:25-32 (1984), Lipsett et al. Recent Prog. Hormone Res. 42:199-246 (1985), Brandon et al. Cancer Res. 49:2203-2213 (1989)), mineral corticoid, progesterone, testosterone, 17.beta.-estradiol (Chrousos et al. J. Clin. Endocrinol. Metab. 58:516-920 (1984)), 1,25-(OH).sub.2 D (Takahashi et al. Biochem S. 227:555-563 (1985)).
Unlike the majority of resistant states described for other steroid hormones and vitamin D in humans, resistance to vitamin D in new world primates does not appear to be related to a mutation in the vitamin D receptor (VDR) protein. Rather, the vitamin D resistant state in new world primates is associated with the apparent high expression of an intracellular vitamin D binding protein (IDBP). IDBP is distinct from members of the serum vitamin D binding protein/albumin families of proteins in that IDBP is cysteine poor. Additionally, while serum vitamin D binding protein/albumin and vitamin D/steroid receptor protein families are principally confined to the extracellular domain and nucleus of the cell, respectively, IDBP predominantly localizes in the cell cytoplasm. However, like these other sterol/steroid binding proteins, IDBP preferentially binds 25-hydroxylated vitamin D metabolites.
IDBP activity has been enriched from extracts of new world primate cells. Nevertheless, numerous attempts to purify IDBP to homogeneity were unsuccessful. Therefore, the precise biochemical characteristics and primary molecular structure of IDBP remained elusive.
By gaining an understanding of the biochemical mechanisms behind vitamin D resistance and the high levels of circulating steroid hormones in new world primates, new opportunities for treating and diagnosing diseases related to either over-production or under-production of vitamin D and other steroidal hormones may be achieved. Such diseases include osteoporosis, hypercalcemia, and vitamin D intoxications.